Abstract D049: Establish patient-derived pancreatic cancer cell organotypic models for personalized drug treatment

Abstract

Abstract Pancreatic cancer (PCa) can vary between individuals, chemotherapy should ideally be tailored to each patient based on the nature of their disease. The detection of potentially chemo-sensitive tumors would significantly improve response rates and facilitate the selection of effective individualized regimens. Developing a method of assessing the likely effectiveness of anticancer drugs using resected tumors of Blacks and whites before treatment will provide PCa patients with a survival advantage. Therefore, we seek to set up patient derived pancreatic cancer organotypic model to test the drug sensitivities. Four patient-derived primary cancer cells from surgically resected Black (2) and White (2) PCa patients were embedded into 3D matrix containing different concentrations of gelatin matrix (3-9%) and transglutaminase (0.1-1.0mg/ml) to mimic tumor microenvironments. Highly and low/dormant 3D conditions were defined based on the cell proliferation rates determined by CCK-8, MTT, and live/dead assays at day 2, 7, 14 days. Cell morphology, colony formation and matrix remodeling were recorded by live imaging due to the 3D matrix transparent nature. Commonly used pancreatic cancer treatment chemo drugs Gemcitabine (Gem), 5-Flu, Capecitabine together with our newly developed Stearoyl-Gem were tested for drug sensitivities in both 2D culture and 3D organotypic cultures. Cell viability, apoptosis, ROS expression, and ATP level in all treatment conditions were imaged and quantitated. The tumor organotypic model mimic two traits of pancreatic tumor microenvironment, including dense extracellular matrix and high transglutaminase expression. Patient derived cancer cells showed significant differences in cell morphology, proliferation, cluster formation in different stiffness microenvironment. We observed patient specific drug sensitivity in 3D cultures. In general, the drug C50 in 3D was shift to higher concentrations when compared with 2D culture. Spontaneous forming tumoroid further in-sensitize drug treatments if we postponed treatment after cell embedding time extended from 48 hours to 144 hours. The cells exhibited delayed drug responses in 3D when compared post treatment 3-day results to 6-day results. Newly developed Stearoyl-Gem showed higher drug potency when compared with Gem. The established patient-derived primary cancer organotypic model provides a platform for testing therapeutic drugs at tumor cell competent and/or dormant conditions. The high throughput 3D model closely mimics tumor microenvironment and may provide a quick turn-around and cost-effective information for patient treatment. Citation Format: Bo Han, Shuqing Zhao, Edward Agyare, Jose Trvino. Establish patient-derived pancreatic cancer cell organotypic models for personalized drug treatment [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D049.